PMID- 34786601
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220405
IS  - 1863-2300 (Electronic)
IS  - 1863-2297 (Print)
IS  - 1863-2297 (Linking)
VI  - 44
IP  - 1
DP  - 2022 Jan
TI  - HLA imputation and its application to genetic and molecular fine-mapping of the 
      MHC region in autoimmune diseases.
PG  - 15-28
LID - 10.1007/s00281-021-00901-9 [doi]
AB  - Variations of human leukocyte antigen (HLA) genes in the major histocompatibility 
      complex region (MHC) significantly affect the risk of various diseases, 
      especially autoimmune diseases. Fine-mapping of causal variants in this region 
      was challenging due to the difficulty in sequencing and its inapplicability to 
      large cohorts. Thus, HLA imputation, a method to infer HLA types from regional 
      single nucleotide polymorphisms, has been developed and has successfully 
      contributed to MHC fine-mapping of various diseases. Different HLA imputation 
      methods have been developed, each with its own advantages, and recent methods 
      have been improved in terms of accuracy and computational performance. 
      Additionally, advances in HLA reference panels by next-generation sequencing 
      technologies have enabled higher resolution and a more reliable imputation, 
      allowing a finer-grained evaluation of the association between sequence 
      variations and disease risk. Risk-associated variants in the MHC region would 
      affect disease susceptibility through complicated mechanisms including 
      alterations in peripheral responses and central thymic selection of T cells. The 
      cooperation of reliable HLA imputation methods, informative fine-mapping, and 
      experimental validation of the functional significance of MHC variations would be 
      essential for further understanding of the role of the MHC in the immunopathology 
      of autoimmune diseases.
CI  - (c) 2021. The Author(s).
FAU - Naito, Tatsuhiko
AU  - Naito T
AUID- ORCID: 0000-0002-2779-4600
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Osaka, Suita, 565-0871, Japan. tnaito@sg.med.osaka-u.ac.jp.
AD  - Department of Neurology, Graduate School of Medicine, The University of Tokyo, 
      Tokyo, Japan. tnaito@sg.med.osaka-u.ac.jp.
FAU - Okada, Yukinori
AU  - Okada Y
AUID- ORCID: 0000-0002-0311-8472
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Osaka, Suita, 565-0871, Japan.
AD  - Laboratory of Statistical Immunology, Immunology Frontier Research Center 
      (WPI-IFReC), Osaka University, Suita, Japan.
AD  - Integrated Frontier Research for Medical Science Division, Institute for Open and 
      Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20211116
PL  - Germany
TA  - Semin Immunopathol
JT  - Seminars in immunopathology
JID - 101308769
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - *Autoimmune Diseases/genetics
MH  - *Genetic Predisposition to Disease
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Major Histocompatibility Complex/genetics
MH  - Polymorphism, Single Nucleotide
PMC - PMC8837514
OTO - NOTNLM
OT  - Autoimmune diseases
OT  - Fine-mapping
OT  - HLA
OT  - HLA imputation
OT  - MHC
COIS- The authors declare no competing interests.
EDAT- 2021/11/18 06:00
MHDA- 2022/04/05 06:00
PMCR- 2021/11/16
CRDT- 2021/11/17 07:01
PHST- 2021/06/11 00:00 [received]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/18 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/11/17 07:01 [entrez]
PHST- 2021/11/16 00:00 [pmc-release]
AID - 10.1007/s00281-021-00901-9 [pii]
AID - 901 [pii]
AID - 10.1007/s00281-021-00901-9 [doi]
PST - ppublish
SO  - Semin Immunopathol. 2022 Jan;44(1):15-28. doi: 10.1007/s00281-021-00901-9. Epub 
      2021 Nov 16.